Document Detail

The anxiogenic drug yohimbine reinstates palatable food seeking in a rat relapse model: a role of CRF1 receptors.
MedLine Citation:
PMID:  16341025     Owner:  NLM     Status:  MEDLINE    
The major problem in treating excessive eating is high rates of relapse to maladaptive eating habits during diet treatments; this relapse is often induced by stress or anxiety states. Preclinical studies have not explored this clinical problem. Here, we adapted a reinstatement model (commonly used to study relapse to abused drugs) to examine the role of stress and anxiety in relapse to palatable food seeking during dieting. Rats were placed on restricted diet (75-80% of daily standard food) and for 12 intermittent training days (9 h/day, every other day) lever-pressed for palatable food pellets (25% fat, 48% carbohydrate) under a fixed ratio 1 (20-s timeout) reinforcement schedule. Subsequently, the rats were given 10 daily extinction sessions during which lever presses were not reinforced, and were then injected with yohimbine (an alpha-2 adrenoceptor antagonist that induces stress and anxiety in humans and non-humans) or given a single food pellet to assess reinstatement of food seeking. The rats rapidly learned to lever press for the palatable pellets and across the training days the ratio of timeout nonreinforced lever presses to reinforced lever presses progressively increased more than three-fold, suggesting the development of compulsive eating behavior. After extinction, yohimbine injections and pellet priming reliably reinstated food seeking. The corticotropin-releasing factor1 (CRF1) receptor antagonist antalarmin attenuated the reinstatement induced by yohimbine, but not pellet priming. Antalarmin also reversed yohimbine's anxiogenic effects in the social interaction test. These data suggest that CRF is involved in stress-induced relapse to palatable food seeking, and that CRF1 antagonists should be considered for the treatment of maladaptive eating habits.
Udi E Ghitza; Sarah M Gray; David H Epstein; Kenner C Rice; Yavin Shaham
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Intramural     Date:  2005-12-07
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  31     ISSN:  0893-133X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-18     Completed Date:  2006-11-01     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2188-96     Citation Subset:  IM    
Behavioral Neuroscience Branch, NIDA/IRP/NIH/DHHS, Baltimore, MD 21224, USA.
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MeSH Terms
Adrenergic alpha-Antagonists / pharmacology*
Anxiety / drug therapy,  physiopathology*
Behavior, Animal / drug effects
Conditioning, Operant / drug effects*
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Interactions
Extinction, Psychological / drug effects
Food Preferences / drug effects*
Interpersonal Relations
Pyrimidines / pharmacology
Pyrroles / pharmacology
Rats, Long-Evans
Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors,  physiology*
Yohimbine / pharmacology*
Grant Support
Z01 DA000434-06/DA/NIDA NIH HHS
Reg. No./Substance:
0/Adrenergic alpha-Antagonists; 0/CRF receptor type 1; 0/Pyrimidines; 0/Pyrroles; 0/Receptors, Corticotropin-Releasing Hormone; 0/antalarmin; 146-48-5/Yohimbine

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